Journal Title
Title of Journal: Mol Cells
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Abbravation: Molecules and Cells
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Publisher
Korean Society for Molecular and Cellular Biology
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Authors: JiYeon Yu JiHae Kim TaeGeum Kim BeomTae Kim YongSuk Jang JeongChae Lee
Publish Date: 2010/08/27
Volume: 30, Issue: 4, Pages: 303-310
Abstract
Growing interest in the beneficial effects of antioxidants has inspired the synthesis of new phenolic acid phenethyl ureas PAPUs with enhanced antioxidant potential We have previously shown the capacity of one PAPU compound E134dihydroxyphenethyl3styrylurea PAPU1 to induce caspasedependent apoptosis in melanoma cells In the present study we examined the antiproliferative effects of PAPU compounds on MCF7 human breast cancer cells and determined the molecular mechanisms involved Treatment with PAPU compounds inhibited predominantly proliferation in these cells where the PAPU1 was the most efficient form Flow cytometric analysis showed that PAPU1 blocked cell cycle progression in the G0/G1 phase and reduced the proportion of cells in G2/M phase This was related to the inhibition of cell cycle regulatory factors including cyclin D/E and cyclindependent kinase CDK 2/4 through induction of p21Cip1 PAPU1 also induced the mitochondrialmediated and caspasedependent apoptosis in MCF7 cells This was evidenced by cellular changes in the levels of Bcl2 and Bax loss of the mitochondrial membrane potential release of cytochrome c into the cytosol and caspase9 activation Collectively our results suggest that G1 cell cycle regulatory proteins and mitochondrial pathways are the crucial targets of PAPU1 in the chemoprevention of breast cancer cells
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